Bovine growth hormone ("BGH") is a polypeptide hormone synthesized in and secreted from the anterior lobe of the pituitary. BGH is believed to be synthesized as a precursor protein (bovine pre-growth hormone) and to be matured to bovine growth hormone during secretion and release of the hormone into the blood stream. Moreover, it has been reported that protein fractions of natural bovine growth hormone include polypeptides that lack a number of amino-terminal amino acids, but which are still biologically active.
A nucleotide coding sequence and an amino acid sequence of bovine growth hormone have been reported [W. L. Miller et al., J. Biol. Chem., 255, pp. 7521-24 (1980); L. J. Hunt and M. O. Dayhoff et al., in "Atlas Of Protein Sequence And Structure", Dayhoff ed., 5, Supp. 2, p. 139 (1976); M. Wallis, FEBS Lett, 35, pp. 11-14 (1973)]. It is a polypeptide of 191 amino acids and appears to be synthesized initially as a bovine pre-growth hormone of 217 amino acids; the signal sequence of 26 amino acids being removed from the N-terminal position during synthesis and secretion [V. R. Lingappa et al., Proc. Natl. Acad. Sci. USA, 74, pp. 2432-36 (1977)].
Growth hormones are normally produced throughout the life cycle, although apparently in higher amounts during the pre-adult period. These hormones are known to promote skeletal growth, nitrogen retention, protein synthesis and to affect glucose and lipid metabolism. Accordingly, growth hormones are recognized as general anabolic agents.
Growth hormones are somewhat species specific. However, a growth hormone from one species may be biologically active in another species lower in the evolutionary scale. Although the mechanism of growth hormone's activity is not well understood, it has been demonstrated that the administration of growth hormone markedly increases the rate of growth, weight gain, and meat production in animals. For example, in one test, the average rate of weight gain in pigs receiving daily injections of purified swine growth hormone was 2.26 pounds per day (as compared to an average weight gain of 2.19 lbs/day in control pigs). More importantly, the treated pigs consumed significantly less feed per day than the control pigs (7.03 lbs as compared to 8.40 lbs). In addition, the treated pigs displayed a marked improvement in carcass quality--the carcasses of the growth hormone-treated pigs averaged 30.57 inches in length and had 1.40 inches of backfat, while those of the control group averaged 29.33 inches in length and had 1.77 inches of backfat. The chemical composition of the edible meat was also markedly improved in the growth hormone-treated animals--13.50% protein, 49.14% moisture and 36.76% fat--as compared to the control group--10.8% protein, 39.43% moisture and 49.27% fat [E. J. Turman, "Some Effects Of Pituitary Anterior Growth Hormone On Swine", Thesis; Purdue University (April 1953)].
Unfortunately, the above-described improved growth and enhanced meat production in animals using growth hormone are not able to be widely realized in catle because there is insufficient BGH available. Today, BGH is extracted from pituitary glands of cattle or produced via recombinant DNA technology in appropriate hosts, e.g., W. L. Miller et al., Journal Biological Chem., 255, pp. 7521-24 (1980), European patent application 47,600 and United Kingdom patent application No. 2,073,245A. Plainly, the former source is not nearly adequate to provide the needed commercial quantities of BGH. The latter source is also not adequate because the expression yields of BGH in various hosts have been too low to provide economically-useful or commercial quantities of BGH.